Rituximab in the Treatment of Patients With Bullous Pemphigoid

April 9, 2013 updated by: Duke University
This study will determine the safety of treatment of bullous pemphigoid in patients resistant to therapy with systemic corticosteroids, with rituximab plus systemic corticosteroids.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized clinically by the presence of severely itchy, tense blisters located over the trunk and extremities. BP is the most common of the autoimmune blistering diseases with an incidence of approximately 10 per 1,000,000 population(1;2). In addition, BP occurs more frequently in the elderly. Routine histopathology reveals a sub-epidermal blister most often with large numbers of eosinophils. Direct immunofluorescence of the skin of patients with BP reveals a linear band of C3 and IgG at the basement membrane zone. Examination of the sera of patients shows the presence of a circulating anti-basement membrane zone autoantibody. This antibody has been found to be directed against a 180 kd protein of the basement membrane zone type XVII collagen (BPAg2) and against a 230 kd protein (BPAg1) found in the epidermal hemi-desmosome(3;4).

BP is a severe disease most often requiring therapy with high dose systemic corticosteroids (0.75 - 1.0 mg/kg/day) often for months(5). In addition, relapses are common and the additional use of immunosuppressive drugs such as azathioprine, methotrexate, cyclosporine A and others are needed to minimize the dose of systemic corticosteroids. The 1-year mortality of BP has been estimated to range from 10 - 30%(1;6). Currently treatment of patients with BP consists of initial use of systemic corticosteroids (0.75 - 1.0 mg/kg/day). Control of symptoms and new blister formation is most often achieved within 1 month and systemic corticosteroids are then tapered. As many as 33 - 50% of patients may not be able to be tapered to clinically acceptable levels of systemic corticosteroids, requiring the addition of systemic immunosuppression often with azathioprine. Approximately 66% of patients require long term treatment with immunosuppressive medication to maintain control of their blistering.(5;7;8) The need for long term systemic corticosteroid therapy often with systemic immunosuppression in an elderly population results in a significant morbidity and mortality in patients with BP. New therapeutic interventions that would potentially allow for the more rapid discontinuation of prednisone, avoidance of systemic immuno- suppression and perhaps earlier clinical relapse would be of substantial benefit to patients with BP. The clinical and laboratory data has demonstrated that BP is an autoantibody mediated blistering disease. Taken together these observations suggest that the use of anti-CD20 antibody (Rituxan) may be useful in the treatment of patients with BP. We have previously treated a patient with BP and graft versus host disease with anti-CD20 and anti-CD25 and were able to achieve clinical and serological remission within 4 weeks of initiation of therapy(9). In addition, others and we have successfully utilized Rituxan for the treatment of pemphigus vulgaris, another autoantibody mediated, autoimmune blistering disease(10-15)

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with autoimmune blistering skin diseases with clinical, histologic and immunological criteria confirming the diagnosis of bullous pemphigoid
  • Ongoing disease activity on 17.5 mg/day of prednisone or more

Exclusion Criteria:

  • Current use of other immunosuppressive therapy such as azathioprine, cytoxan or mycophenolate mofetil within the last 4 weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Rituximab
Open label study all subjects treated with rituximab
Drug: Rituximab
Infusion of 1000 mg of rituximab on day 0 and day 14
Other Names:
  • rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Safety Endpoint
Time Frame: 1 year
The primary safety endpoint is the occurrence of treatment emergent adverse events including infections, infusion reactions and disease progression. These were determined by clinical evaluation and laboratory questions. Disease progression is defined as development of new blisters despite therapy. These are reported as the number of participants with a study related SAE.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Days to Cessation of New Blister
Time Frame: 1 year
The first study visit in which patient reported and was confirmed to have no new blister or lesion formation .
1 year
Systemic Corticosteroid Dose of 25% of Starting Dose or 10 mg/Day by Week 24
Time Frame: 24 weeks
Subject systemic corticosteroid dosage at week 24 was 25% of starting dose or 10 mg/day of prednisone or less
24 weeks
IgG Anti Bullous Pemphigoid (BP) 180 Measured in Units by ELISA at Week 24.
Time Frame: Week 0 and at 24 weeks
IgG antibodies against BP 180 measured in units (by ELISA) for each participant at week 0 compared to value at week 24,
Week 0 and at 24 weeks
B Cell Number at Week 24
Time Frame: Week 0 and at 24 weeks
Peripheral blood B cell number at week 24 compared to B cell number at week 0
Week 0 and at 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Russell Hall, III, MD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

February 1, 2006

First Submitted That Met QC Criteria

February 1, 2006

First Posted (Estimate)

February 3, 2006

Study Record Updates

Last Update Posted (Estimate)

April 11, 2013

Last Update Submitted That Met QC Criteria

April 9, 2013

Last Verified

September 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00013763

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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